CT scans in sub-groups of chronic schizophrenics

Measurements of the ventricular brain ratio (VBR), width of the sylvian fissure, and symmetry of the frontal lobes were obtained from 26 chronic schizophrenic patients, 22 alcoholic and neurological patients, and 20 normal controls. All schizophrenic subjects were non-responsive to long-term neuroleptic medication for 3–25 yr and were between 23 and 45 yr of age. Detailed diagnostic workups differentiated two sub-groups by DSM III criteria, residual and paranoid. The former group was characterized by large VBRs while the paranoids were within the range of normal controls. Those patients with VBRs greater than nine had wider sylvian fissures and increased frequency of reversed frontal asymmetry. As a group, the VBRs of all schizophrenics differed significantly from normal controls but did not differ from those of alcoholics or patients with neurological disorders (migraine, generalized seizures). This finding indicates that DSM III criteria applied to CT scan measures may help define a sub-group within the schizophrenias.

While not specific to this disorder, the underlying pathology demonstrating increased VBRs and other CT scan changes may be specific to but different from other disorders.     

Selective enlargement of the third ventricle found in chronic schizophrenia

Selective enlargement of the third ventricle was observed when the area and the VBR (ventricle-brain ratio) were measured in 37 chronic schizophrenics (DSM-III criteria) as compared with 37 controls. However, the width or the width to IS (maximum inner skull width) ratio was not significantly different between the two groups. There was no correlation between any measure of the third ventricle and any of the clinical variables. Five patients had VBRs of the third ventricle that were larger than the mean + 2 SD of the control, but there was no significant difference between these five schizophrenics and the others in any of the clinical variables.     

Clinical and neuropsychological correlates of cerebral ventricular enlargement in schizophrenia

A comprehensive assessment of computed tomography (CT) with respect to clinical, historical and neuropsychological variables has been carried out in a sample of DSM III schizophrenics fairly heterogenous with respect to duration and severity of illness and in a normal control group matched for sex, age and educational level.

The mean value of ventricular brain ratio (VBR) was significantly higher in schizophrenics than controls. Seven patients (21.2%) who had VBRs exceeding 2 SD of the control mean showed a significantly longer duration of illness than the other schizophrenics with significantly higher scores on the subscales alogia, effective flattening and attentional impairment of SANS, on the scales self-care and behaviour in crises and emergencies of DAS, on the scales rhythm, tactile, visual, reading, arithmetic, memory and left hemisphere of LNNB, and on the subtests arithmetic, digit span, digit symbol and block design of WAIS.

These results confirm earlier reports of an enlargement of lateral cerebral ventricles in a subset of schizophrenics, and its association with a higher degree of cognitive and neuropsychological impairment, social maladjustment and defectual symptomatology. Moreover, they suggest that the neuropathological process likely to underlie the increase of cerebral ventricular size progresses during the course of the illness rather than predating its onset.     

An association between reduced interhemispheric EEG coherence in the temporal lobe and genetic risk for schizophrenia

Previous studies have suggested that schizophrenic patients show resting changes such as frequency-slowing and decreased coherence in the frontal and temporal area. We sought to determine whether these findings are also found in clinically unaffected siblings of schizophrenics and estimate heritability by calculating relative risk. We investigated two independent data sets: (1) from the NIMH St. Elisabeth's campus (59 schizophrenics, 76 unaffected siblings and 32 unrelated normal controls) and (2) from the NIH-campus (Bethesda) (59 schizophrenics, 90 unaffected siblings and 26 unrelated normal controls). We computed power spectra and coherence on the first data set and then tried to replicate the results on the second data set. Power spectrum analysis suggested that schizophrenics are cortically hypoactivated, whereas in unaffected siblings, a tendency for hyperactivation was found. In contrast, spectral coherences (0.5-5Hz) were reduced in both data sets in the temporal lobe areas in schizophrenics and in their unaffected siblings. Changes were most pronounced for the interhemispheric coherence linking both posterior temporal lobe areas. Relative risk calculations (lambda(S)) ranged between 3.7 and 9.8, depending on phenotype definition. Thus, while power spectrum EEG abnormalities may be state-dependent, reduced coherence as a possible measure of neuronal synchronization is familial and potentially a heritable trait related to genetic risk for schizophrenia.     

Clinical correlates of lateral ventricular enlargement in bipolar affective disorder

The presence of lateral ventricular enlargement in some manic-depressive subjects, as assessed by ventricular-brain ratios (VBRs), has been reported. A study of 27 bipolar patients and 27 individually matched normal controls confirmed that finding. Bipolar patients had significantly larger VBRs than did controls. Clinical measures associated with the presence of ventricular enlargement in the bipolar patients included more frequent hospitalizations and histories of persistent unemployment. Other measures of illness severity or social deterioration were not significantly associated with large VBR.     

Ventricular enlargement in teenage patients with schizophrenia spectrum disorder

Recent research has demonstrated statistically significant differences between the ventricular-brain ratios (VBRs) of schizophrenic patients and control subjects. In this study the VBRs of teenage schizophrenic/schizophreniform patients (N = 15) and borderline patients (N = 8) were measured and compared with those of controls of similar ages (N = 18). The schizophrenic group had significantly larger ventricles than the other two groups (p less than .0001). These findings support the hypothesis of previous investigators that ventricular enlargement is present early in the course of schizophrenia.     

Hippocampal deformities in the unaffected siblings of schizophrenia subjects.

BACKGROUND: Neuroanatomical abnormalities have been reported in schizophrenia subjects and their relatives and may be related to genetic vulnerability. The objective of this study was to further elucidate hippocampal deformities as a marker of genetic vulnerability for schizophrenia. METHODS: Magnetic resonance scans were collected in 13 pairs of schizophrenics and their unaffected siblings from families with multiple affected members, in 12 schizophrenics from families without another affected member, and in 10 healthy controls. Hippocampal volume and shape were compared using large-deformation high-dimensional brain mapping. RESULTS: Decreases in hippocampal volume, covaried for total cerebral volume, were observed in the schizophrenia subjects from families with multiple affected members, as well as in their unaffected siblings. Shape analysis demonstrated that both groups of schizophrenia subjects, as well as the unaffected siblings, could be distinguished from the controls; however, no significant difference in hippocampal shape was found between the schizophrenia subjects and their unaffected siblings. Visualization of the pattern of hippocampal shape deformity in both groups of schizophrenia subjects and in the unaffected siblings showed inward deformities of the head of the hippocampus. CONCLUSIONS: Deformations of hippocampal anatomy may be related to the genetic vulnerability of acquiring schizophrenia.     

Neurological dysfunctioning in offspring of schizophrenics in Israel and Denmark. A replication analysis

Neurological functioning was compared in children at risk for schizophrenia from samples recruited in Israel and Denmark. In both samples neurological signs were assessed in school-age children with one schizophrenic parent and a matched group of children with no mentally ill parents. Multidimensional Scalogram Analysis of data identified, in both samples, a radex structure of neurological functioning, radiating from motor to sensory-perceptual signs. In both samples, the gradient of neurological functioning differed between the offspring of schizophrenics and controls. For both the offspring of schizophrenics and controls, the largest number of children showed no or few signs of neurological dysfunctioning. A subgroup of the offspring of schizophrenics, but not the controls, showed multiple signs of neurological dysfunctioning that varied in pattern among individuals.     

Parental communication deviance and forms of thinking in male schizophrenic offspring

In a step beyond earlier research on parental communication deviance (CD) and schizophrenia, more specific links between these phenomena were investigated. First, subtypes of schizophrenia were distinguished by amount of formal thought disorder, and two forms of parental CD--called the "disorganized" and the "evasive" types--were qualitatively distinguished. In a sample of young adult male patients, it was found that schizophrenics who manifested definite and severe formal thought disorder had parents with much CD in their speech (especially the disorganized type). In contrast, male paranoid schizophrenics with constricted forms of thinking had parents whose level of CD was lower (and was comparable to that of the parents of the nonschizophrenic controls). This suggests that parental CD may be better understood as specifically associated with cognitive disorganization in the offspring, rather than with overall DSM-III or DSM-II criteria for schizophrenia.     

Neurologic abnormalities in schizophrenic patients and their families. II. Neurologic and psychiatric findings in relatives

Neurologic abnormalities in 21 nonschizophrenic siblings and parents of schizophrenics, 24 DSM-III schizophrenics, and 24 normal "control" subjects were assessed by experienced neurologists blind to the subjects' psychiatric status. Medication artifacts and other neurologic signs likely to be etiologically irrelevant to psychiatric illness were excluded. Psychiatric diagnostic assessments of subjects were made blind to neurologic results. The prevalence of neurologic abnormalities in relatives was significantly greater than in controls, but similar to that among the schizophrenics. Relatives and controls differed even more markedly on signs involving motor system abnormalities of localizing significance. Finally, the relatives showed a suggestive dissociation of psychopathology and neurologic signs. The results appear most consistent with the hypothesis that overt schizophrenia may often result from the combined operation of two independent familial factors--one "psychopathologic," the other "neurologic".     

Offspring of schizophrenics. III. Hyperactivity and neurological soft signs.

Twenty-nine male offspring of "continuous schizophrenics" (chronic, borderline, and chronic schizoaffective schizophrenics), plus controls, were given neurological and psychological examinations at age 7. Eight of the 29 were found to have high ratings on a factor score that was termed "hyperactive" (increased activity, impulsivity, distractibility, and emotional lability), and three of these boys had high ratings for neurological signs as well. These frequencies were significantly greater than the control values. Mild incoordination, such as awkwardness in performing rapidly alternating movements, was the neurological soft sign most elevated in the index group. Fifteen female offspring of schizophrenics were not found to differ from their controls on these measures. Previous studies of the childhood of male schizophrenics have found behavior patterns similar to the behavior of the boys who scored high on our hyperactive factors. It is thus likely that the "hyperactive cases" in this sample are even more at risk for developing schizophrenia in later life than the other offspring of schizophrenic parents.     

Abnormal Rich-Club Organization Associated with Compromised Cognitive Function in Patients with Schizophrenia and Their Unaffected Parents

Schizophrenia is considered to be a disorder of brain connectivity, which might result from a disproportionally impaired rich-club organization. The rich-club is composed of highly interconnected hub regions that play crucial roles in integrating information between different brain regions. Few studies have yet investigated whether the structural rich-club organization is impaired in patients and their first-degree relatives. In this study, we established a weighted network model of white matter connections using diffusion tensor imaging of 19 patients and 39 unaffected parents, 22 young healthy controls for the patients, and 25 old healthy controls for the parents. Feeder edges between rich-club nodes and non-rich-club nodes were significantly decreased in both schizophrenic patients and their unaffected parents compared with controls.Furthermore, the feeder edges showed significant positive correlations with the scores in Category Fluency Test—animal naming in the unaffected parents. Specific feeder edges exhibited discriminative power with accuracy of 84.4% in distinguishing unaffected parents from old healthy controls. Our findings suggest that impaired richclub organization, especially impaired feeder edges, may be related to familial vulnerability to schizophrenia,possibly reflecting a genetic predisposition for schizophrenia.     

Reduction of Cerebral Blood Flow in Chronic Schizophrenia: Relation to Age

Abstract: The effect of age on resting-state cerebral blood flow (CBF) was studied in 40 medicated patients with chronic schizophrenia aged 20 to 57 and 32 age- and sex-matched normal Controls, using the regional CBF with the xenon-133 inhalation technique. Global CBF (average of 16 cerebral regions) and the left prefrontal flow ratio (left prefrontal/global CBF) were significantly lower in schizophrenics aged 20–29 than in age-matched controls. Both global CBF and the left prefrontal flow ratio correlated with age in controls, but neither of such correlations was found in schizophrenics. Therefore, the CBF deficits in chronic schizophrenia appear to be unaffected by the aging process.     

Obstetric complications in siblings of Japanese schizophrenics: data from the Maternal and Child Health Handbook

Although the precise etiology of schizophrenia remains unknown, the development of schizophrenia has been associated with a history of obstetric complication (OC). Furthermore, some studies show structural and functional brain abnormalities in the unaffected siblings of schizophrenics. In this study the perinatal histories of 18 unaffected siblings of schizophrenics and 15 unrelated healthy controls, as detailed in their mothers' Maternal and Child Health Handbook records, were retrospectively analyzed. Records were scored for obstetric complication by the method developed by [Parnas, J., Schulsinger, F., Teasdale, T.W., Shulsinger, H., Feldman, P.M., Mednick, S.A., 1982. Perinatal complications and clinical outcome within the schizophrenia spectrum. Br. J. Psychiatry 140, 416-420]. The authors found the sibling group had greater pregnancy and birth complication (PBC) frequency, severity and total scores than the control population.     

The relationship between performance and fMRI signal during working memory in patients with schizophrenia, unaffected co-twins, and control subjects

While behavioral research shows working memory impairments in schizophrenics and their relatives, functional neuroimaging studies of patients and healthy controls show conflicting findings of hypo- and hyperactivation, possibly indicating different relationships between physiological activity and performance. In a between-subjects regression analysis of fMRI activation and performance, low performance was associated with relatively lower activation in patients than controls, while higher performance was associated with higher activation in patients than controls in DLPFC and parietal cortex, but not occipital cortex, with unaffected twins of schizophrenics being intermediate between the groups. Accordingly, this supports the idea that both hyper and hypoactivation may be possible along a continuum of behavioral performance in a way consistent with a neural inefficiency model. Further, this study offers preliminary evidence that the relationship between behavior and physiology in schizophrenia may be heritable.     

Increased number of offspring in first degree relatives of psychotic individuals: a partial explanation for the persistence of psychotic illnesses

Objective: As patients with psychotic illness have fewer offspring than controls, the persistence of psychotic illness is puzzling. We hypothesized that unaffected first‐degree relatives of patients have more offspring than controls. Method: Probands were 4904, individuals with non‐affective psychotic disorders identified from a hospitalization registry. Unaffected first degree relatives and matched controls were identified from the Israeli Population Registry. The number of offspring of unaffected parents, biological siblings and controls was ascertained. Results: Unaffected parents of psychotic patients had more offspring/person than controls; 4.5 ± 2.7 vs. 3.4 ± 2.2, P = 0.000. Unaffected parents from familial psychosis families (more than one affected family member) had 1.83 more offspring than controls; unaffected parents from non‐familial psychosis families had 0.97 more offspring than controls (both P < 0.001). Conclusion: These findings might imply that genes which increase susceptibility for schizophrenia may be associated with increased number of offspring, perhaps supplying a partial explanation for the persistence of psychosis.     

Declarative memory in unaffected adult relatives of patients with schizophrenia: a systematic review and meta-analysis

Despite evidence for diverse neuropsychological impairment in schizophrenia, verbal declarative memory has emerged as a core deficit in the disorder. Similar but less marked impairments have been demonstrated in unaffected biological relatives of patients with schizophrenia, but the nature and extent of the memory impairment in relatives compared to controls is unclear. We have conducted a systematic review and meta-analysis of the literature investigating declarative memory in unaffected biological relatives of schizophrenics and controls, with the aim of quantifying memory deficits in relatives. The standardised mean difference between groups was calculated for nine measures of declarative memory and two measures of intellectual ability, based on 21 studies of several hundred relatives of schizophrenics and controls. Unaffected relatives showed poorer performance relative to controls on all tests of memory examined. Small to moderate effect sizes, with overlapping 95% confidence intervals, were greatest on immediate (trial 1) list recall (0.65), followed by immediate (0.53) and delayed story recall (0.52). Verbal and general IQ showed smaller standardised mean differences as the latter tests, while the smallest standardised mean difference was shown on delayed visual recall (0.32). Results suggest greater deficits on tests of increasing memory load or which place demands on effective encoding processes but more studies with these tasks are needed. Investigation of sub-groups within these cohorts (e.g. age groups within or beyond the maximum age of risk) is recommended in order to identify deficits specific to the disease process.     

Schizophrenic patients and their parents. A multimethod design and the findings from an illustrative empirical study of cognitive disorders and communication deviances

The research design and main findings from a multimethod research project, in which cognitive disorders in schizophrenic patients and communication deviances in their parents were examined, are presented. Non-paranoid schizophrenics manifested cognitive disturbances on a majority of the variables examined, while paranoid schizophrenics did not. Likewise, parents of non-paranoid schizophrenics revealed significantly more communication deviance than parents of paranoid schizophrenics as well as the control groups (normal and "neurotics"). Egocentrism appeared to be a prominent characteristic of the communication of non-paranoid schizophrenics' parents. Conspicuous among the cognitive deficits in their offspring were attentional disturbances. Support for the existence of a link between the parents' communication and the offsprings' cognitive functioning was found by correlation- and regression analyses.     

Episodic and residual thought pathology in chronic schizophrenics: effect of neuroleptics

We sought to determine the effect of neuroleptic treatment on thought disorder in chronic schizophrenics, using the Thought Disorder Index (TDI). We were able to demonstrate that high levels of thought disorder are found in chronic schizophrenic and schizoaffective patients, while in both bipolar patients and normal controls thought pathology is minimal. Moreover, the TDI appears to be particularly well suited to the characterization of thought disorder in chronic schizophrenics. For total scores on the TDI, we were unable to demonstrate a significant reduction in thought pathology, although it was evident that thought disorder as reflected in the Conceptual Disorganization and Unusual Thought Content subscales of the Brief Psychiatric Rating Scale is significantly reduced by neuroleptics. In analyses of subscores of the TDI reflecting four levels of severity, we were able to show that more severe forms of thought pathology are normalized by neuroleptics, while less severe pathology is largely unaffected. Our results suggest that neuroleptic treatment reduces thought pathology associated with acute episodes, but that somewhat milder, though still disabling, residual thought pathology persists after clinical remission has been attained.